PhoQ is an unsaturated fatty acid receptor that fine-tunes Salmonella pathogenic traits

CARABAJAL, MARÍA AYELÉN; VIARENGO, GASTÓN; YIM, LUCÍA; MARTÍNEZ-SANGUINÉ, ADRIANA; MARISCOTTI, JAVIER F.; CHABALGOITY, JOSÉ A.; RASIA, RODOLFO M.; GARCÍA VÉSCOVI, ELEONORA

Science Signaling

American Association for the Advancement of Science

Lugar: Washington; Año: 2020 vol. 13

1945-0877

*The two first authors contributed equally to this work. Salmonella enterica PhoP/PhoQ signal transduction system coordinates the spatiotemporal expression of key virulence phenotypes that confer pathogenic traits to these bacteria. By NMR analysis, we now reveal that PhoQ is the Salmonella receptor for LCUFAs which exert their action by imposing a conformational alteration on the periplasmic domain of the PhoQ protein. This finding elucidates the first signal transduction step triggered by environmental LCUFAs that results in repression of PhoQ autokinase activity and explains the downstream down-regulation of the PhoP/PhoQ-dependent genes expression. Using linoleic acid (LA) as an archetypal ligand, we reveal that recognition of LCUFAs by PhoQ is not stereospecific, being positional or geometrical isomers of LA equivalently proficient in PhoQ autophosphorylation inhibition. In addition, we show that LCUFAs detection by PhoQ is conserved in Salmonella enterica serovars other than Typhimurium. Orally acquired Salmonella encounters conjugated LA (CLA) in the human intestine as product of metabolic conversion of dietary LA by microbiota. Therefore, we combined the streptomycin pre-treated mice model for serovar Typhimurium colitis with short-term oral administration of CLA. In CLA-treated mice, wild-type Salmonella phenocopied the phoP mutant enhanced levels of gut colonization. Consistently, CLA administration resulted in an increased capacity of wild-type Salmonella to reach mice spleens. In contrast, the well-known inability to disseminate systemically of the phoP strain remained unchanged irrespective of mice treatment. Altogether, our results reveal that, by signaling on PhoQ, environmental LCUFAs finely-tune the fate of Salmonella throughout the infection process. This knowledge will also aid in the design of novel anti-Salmonella therapies.